Inhibition of pathophysiological proteases with novel quercetin derivatives

Abstract

Novel quercetin derivatives were prepared to change its physicochemical properties and effects on activity of proteolytic enzymes. For them preparation, the selective protection procedures some of the quercetin hydroxyl groups and acylation of the others with acylchlorides were used. The ability of these compounds to inhibit the activity of serine proteases e.g. trypsin, thrombin, urokinase and elastase was studied. In micromolar range, tested derivatives were the most potent inhibitors of thrombin. There was estimated better inhibition of thrombin for prenylated, acetylated, feruloyl and caffeoyl quercetin esters. Slight inhibitory effect of all quercetin derivatives on elastase was found. Among tested derivatives only diquercetin displayed better inhibiton. Trypsin and urokinase were inhibited by quercetin at comparable level. Slight improvement in inhibitory effect of trypsin and urokinase was seen for chloronaphtoquinone quercetin that revealed enhanced inhibiton of thrombin, too. However, no infl uence on elastase activity was determined for this compound. Obtained results indicate that certain modifi cations of quercetin structure could improve its biological properties.

The Role of Dietary Phenolic Compounds in Protein Digestion and Processing Technologies to Improve Their Antinutritive Properties

“…EGCG binding to trypsin (Ka 1.82 × 10 5 at 37 °C) results in slight protein stabilization with increased β‐sheet and decreased random content (Wu and others ). Quercetin derivatives were found to inhibit trypsin, with quercetin having 10 times higher potency than 4‐guanidinobenzoic acid, the standard serine protease inhibitor (Danihelová and others ). Acerola bagasse flour extracts, rich in EC, siringic acid, catechin, EGCG, gallic acid p ‐cumaric acid, have also been shown to slightly inhibit trypsin (Marques and others ).…”

“…Kinetic parameters indicate that the inhibition of elastase by polyphenols is reversible and competitive. Quercetin and some of its derivatives have also shown slight inhibitory activity toward elastase (Danihelová and others ). Crude grape pomace extract, with catechin, EC, and procyanidins B1 and B2 as major polyphenols, showed dose‐dependent inhibitory activity against collagenase and elastase activity, with the fraction containing hydrophilic low‐molecular weight polyphenols, in particular gallic acid, the most effective (Wittenauer and others ).…”